PROJECT SUMMARY/ABSTRACT Cognitive control is implicated in a number of higher-order cognitive abilities, including the allocation and maintenance of attention, task switching and response selection. Individual ability to engage these functions is variable, and deficits in these areas can lead to significantly diminished quality of life. Repetitive head impacts (RHI) are linked to the development of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease characterized by aberrant tau protein deposition that currently can only be diagnosed at autopsy. Individuals at risk for and later diagnosed with CTE often display deficits of cognitive control that are observable behaviorally and via neurocognitive tests (NCT). Participants in high impact sports (e.g., American football, boxing, rugby) and military service-members often experience a large number of repetitive head impacts (RHI). The current lack of in vivo biomarkers to evaluate the long-term effects of RHI severely impacts the ability of researchers and clinicians to monitor at risk individuals for the development and progression of CTE. The research proposed herein aims to characterize the link between cognitive control network function, normal and abnormal functional network connectivity and NCT performance, and whether this is predictive of exposure to RHI. The proposed methods and hypotheses within this research proposal also provide a valuable training opportunity. Preliminary results from our laboratory demonstrate that a subject's functional connectivity fingerprint can predict individual task fMRI activation. Furthermore, preliminary results in a dataset of retired NFL players indicate aberrant functional connectivity within the dorsal attention and cognitive control networks. The proposed series of studies will employ functional MRI (fMRI), resting state functional connectivity (RSFC), and NCT to: 1) examine the relationship between cognitive control and attention fMRI activation, network RSFC and the effect of RHI exposure; and 2) investigate the relationship between fMRI, functional connectivity and diminished NCT performance in a population exposed to RHI. We propose to first study a group of healthy control subjects to increase our knowledge of how the brain engages control processes in auditory and visual attention tasks, and relate this to existing, well-accepted tests of attention and cognitive control. Subsequently, we will investigate the relationship between diminished cognitive control processes and altered functional connectivity in a population exposed to RHI. Our aim is to establish the predictive power of RSFC for individual variability in the application of cognitive control processes in everyday life. Importantly, the successful completion of this study will increase our understanding of long term effects of RHI on the brain's connectivity and begin to formulate clinical profiles that may be used in the diagnosis and staging of CTE in vivo